Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress- related signaling pathways.

BACKGROUND: Recent reports suggested the involvement of oxidative stress- and endoplasmic reticulum stress (ERS)-associated pathways in the progression of ischemia/reperfusion (I/R) injury. Notoginsenoside R1 (NGR1) is a novel saponin isolated from P. notoginseng, which has a history of prevention and treatment of cardiovascular diseases.

OBJECTIVE: We aimed to examine the cardioprotective effects of NGR1 on I/R-induced heart dysfunction ex vivo and in vitro.

METHODS: H9c2 cadiomyocytes were incubated with NGR1 for 24 h and exposed to hypoxia/reoxygenation. Isolated rat hearts were perfused by NGR1 for 15 min and then subjected to global ischemia/reperfusion. Hemodynamic parameters were monitored as left ventricular systolic pressure (LVSP), heart rate, and maximal rate of increase and decrease of left ventricular pressure (± dP/dt max/min).

RESULTS: NGR1 pretreatment prevents cell apoptosis and delays the onset of ERS by decreasing the protein expression levels of ERS-responsive proteins GRP78, P-PERK, ATF6, IRE, and inhibiting the expression of pro-apoptosis proteins CHOP, Caspase-12, and P-JNK. Besides, NGR1 scavenges free radical, and increases the activity of antioxidase. NGR1 inhibits Tunicamycin-induced cell death and cardiac dysfunction.

CONCLUSION: We elucidated the significant cardioprotective effects of NGR1 against I/R injuries, and demonstrated the involvement of oxidative stress and ERS in the protective effects of NGR1.